Effect of Botulinum-A Toxin Injection into Bulbospongiosus Muscle on Ejaculation Latency in Male Rats

Abstract

Introduction Premature ejaculation (PE) is the most common male sexual dysfunction. A variety of pharmacotherapeutic strategies have been employed to treat men suffering with lifelong PE. However, there are currently no pharmaceuticals approved by the U.S. Food and Drug Administration specifically designed for PE treatment. Aim Given that the bulbospongiosus muscle is involved in the ejaculatory reflex in both humans and rodents and that local administration of botulinum-A can abolish muscle contractions, the current study examined the effect of injection of botulinum-A toxin into the bulbospongiosus muscle on the ejaculatory latency of male rats. Methods After screening for normal sexual activity with sexually receptive female rats, 33 sexually experienced male Long-Evans rats (Harlan Laboratories, Indianapolis, IN, USA) underwent an additional four pretreatment sexual exposures over the course of the following week, during which all components of sexual behavior were video recorded by trained observers. On the day after their fourth experience, rats were anesthetized and received a single injection of either 0.5 unit (n = 11) or 1 unit (n = 11) of botulinum-A toxin or saline vehicle (n = 11). Botulinum-A toxin was dissolved in 0.1 mL of saline vehicle and injected bilaterally into the bulbospongiosus muscle by the percutaneous route. Beginning 2 days after treatment, sexual behaviors were reexamined over the course of the following week on four separate occasions. Main Outcome Measures The latency to achieve ejaculation, and the frequencies and latencies of mounts and intromissions were video recorded by trained observers in a blinded fashion. Results Relative to pretreatment measurements, bilateral injection of saline vehicle into the bulbospongiosus muscle did not affect ejaculation latencies. However, rats treated with either 0.5 or 1 unit of botulinum-A toxin exhibited significantly longer latencies to achieve ejaculation relative to pretreatment performance. Of note, botulinum-A toxin did not affect the ability to achieve mounts, intromissions, or ejaculation. Conclusions These results demonstrate that botulinum-A toxin injection into the bulbospongiosus muscle is a safe and effective treatment that extends ejaculatory latency in rats without affecting the ability to engage in sexual activity or achieve ejaculation. Further studies are required to evaluate this therapeutic concept in PE patients.

Emerging and investigational drugs for premature ejaculation

“…He subsequently demonstrated that percutaneous injection of either 0.5 or 1 unit Botulinum toxin A into the bulbospongiosus muscle bilaterally significantly increased ejaculatory latency in male rats (0.5 unit: 314.6±193.1 to 507.6±277.8 s, P=0.021; 1 unit: 264.4±129.1 to 598.2±352.5 s, P=0.008) in a dose-dependent manner compared to pre-treatment latency without affecting their ability to achieve mounts, intromissions, or ejaculation (156). Mean ejaculation latency reached its peak 11 days after injection and decreased sharply 14 days after injection at both doses.…”

New Therapeutic Perspectives in Premature Ejaculation

“…Nevertheless, further studies in humans are essential to evaluate and corroborate a PE potential benefit of botulinum-A toxin injection in bulbospongiosus muscle [34].…”

“…Despite the bilateral injection did not produce a significant impact on ejaculation latencies, rats treated with either 0.5 or 1 unit botulinum-A toxin exhibited significantly longer ejaculatory latencies compared with their pretreatment performance. According to the study, the ejaculation latency reached its peak 11 days after injection and decreased sharply 14 days after injection [34].…”

“…Moreover, Botulinum-A toxin muscle injections wouldn't cause local or systemic side effects, as witnessed with topical creams and SSRI treatments [34].…”

Botulinum toxin in urology: a review of clinical potential in the treatment of urologic and sexual conditions

“…Animal model has shown that BoNT-A injection into the bulbospongiosus muscle is a safe and effective treatment that extends ejaculatory latency in rats without affecting the ability to engage in sexual activity or achieve ejaculation [76]. Currently, a Phase II trial is being conducted to examine the safety and efficacy of BoNT-A for the treatment of premature ejaculation [77] and at this stage, it is too early to adopt BoNT injection as a valid treatment for premature ejaculation.…”